1. The Hidden Epidemic of Isoniazid-Resistant Tuberculosis in South Africa.
- Author
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Klopper, Marisa, van der Merwe, Charnay J., van der Heijden, Yuri F., Folkerts, Megan, Loubser, Johannes, Streicher, Elizabeth M., Mekler, Kate, Hayes, Cindy, Engelthaler, David M., Metcalfe, John Z., and Warren, Robin M.
- Subjects
WHOLE genome sequencing ,ISONIAZID ,TUBERCULOSIS ,GENOTYPES ,PHENOTYPES - Abstract
Rationale: Isoniazid-resistant tuberculosis (Hr-TB) is often overlooked in diagnostic algorithms because of reliance on first-line molecular assays testing only for rifampicin resistance. Objectives: To determine the prevalence, outcomes, and molecular mechanisms associated with rifampin-susceptible, isoniazid-resistant TB (Hr-TB) in the Eastern Cape, South Africa. Methods: Between April 2016 and October 2017, sputum samples were collected from patients with rifampin-susceptible TB at baseline and at Weeks 7 and 23 of drug-susceptible TB treatment. We performed isoniazid phenotypic and genotypic drug susceptibility testing, including FluoroTypeMTBDR, Sanger sequencing, targeted next-generation sequencing, and whole-genome sequencing. Results: We analyzed baseline isolates from 766 patients with rifampin-susceptible TB. Of 89 patients (11.7%) who were found to have Hr-TB, 39 (44%) had canonical katG or inhA promoter mutations; 35 (39%) had noncanonical katG mutations (including 5 with underlying large deletions); 4 (5%) had mutations in other candidate genes associated with isoniazid resistance. For 11 (12.4%), no cause of resistance was found. Conclusions: Among patients with rifampin-susceptible TB who were diagnosed using first-line molecular TB assays, there is a high prevalence of Hr-TB. Phenotypic drug susceptibility testing remains the gold standard. To improve the performance of genetic-based phenotyping tests, all isoniazid resistance–associated regions should be included, and such tests should have the ability to identify underlying mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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